Biomedical science最新文献

Three kinds of monoclonal antibody (Mab) of different specificity have been obtained against the N-terminal disulphide knots of fibrinogen and fibrin. Their effects on different phases of fibrin polymerization have been studied. These antibodies were shown to be directed against different epitopes of the B beta(1-53) fragment of the fibrinogen molecule. The different Mab had different effects both on the rate of protofibril lateral aggregation and on the final turbidity of fibrin clots. The Mab were of three specificities: (1) those from clone 2d-2a inhibited the rate of lateral aggregation of protofibrils and decreased the turbidity of the final clot; (2) those from clone B-4C accelerated the polymerization step but did not affect clot turbidity: and (3) those from clone D-IB did not have any effect on either fibrin polymerization or final clot turbidity. The localization of the epitopes recognized by all three kinds of Mab and analysis of our own data and those of others allow us to conclude that one of the active loci involved in protofibril lateral association is situated in the B beta(15-53) fragment of the fibrinogen molecule. Fibrinopeptide B does not need to be split off for this site to function. Fibrin polymerization can occur when one of the two sites of protofibril lateral aggregation in dimeric fibrin molecules is blocked by Mab, and the final clot turbidity is then reduced. The splitting off of one of the two fibrinopeptides B in fibrinogen molecules by thrombin can take place even when the second B beta(Arg14-Gly15) bond is blocked by an antibody molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of the target cells for the immunomodulatory action of muramyl dipeptide (MDP) was addressed by investigation of various B-cell and T-cell lines. The lines used were: IM-9, a human lymphoblastoid B-cell line that spontaneously produces IgG; EL-4, a murine T-cell line that produces interleukin-2 (IL-2) on stimulation with phorbol myristate acetate; and CTLL-2, an IL-2-dependent murine T-cell line. MDP was shown to modulate such T-cell and B-cell functions as cell proliferation and secretion of IL-2 and IgG, respectively, in vitro. The effect of MDP in vitro was determined by both MDP dose and the control level of cell activity. The evidence obtained supports the possibility of the direct action of MDP on T and B lymphocytes.

The combination of two epileptogenic factors--rhythmic photostimulation at frequencies of 5-6 Hz, and local injury to the visual cortex by freezing--were used to induce paroxysmal spike-and-wave type activity in rabbits. This activity (5-6 discharges per second) was observed near the injured site, as well as in the mirror foci, but it never extended to the frontal cortex. Spike-and-wave discharges were also observed in the lateral geniculate body and the superior colliculus. Diazepam completely inhibited this epileptic activity, but pentylenetetrazol and caffeine potentiated its manifestation. The dominant theta-rhythm frequency coincides with the main electroencephalogram synchronization frequency, and with the frequency of rhythmical photostimulation which was able to induce the seizures. These findings are discussed with respect to the theory of synchronization of biorhythms in the brain.

The functional state of internalized epidermal growth factor (EGF) receptors is reviewed. It is shown that in A431 cells internalized EGF-receptor complexes remain in an undissociated and nondegraded state for a long time. The internalized EGF-receptor complexes retain activated tyrosine kinase activity capable of autophosphorylation and phosphorylation of exogenous substrates. It is concluded that the activated tyrosine kinase of growth factor receptors is translocated from the plasma membrane into the cytoplasm and that the activated state is maintained for long enough to allow phosphorylation of intracellular substrates which may be inaccessible to the kinase while the latter is associated with the membrane.

The responses of sensorimotor cortical neurons in hungry and in fed rabbits to stimulation of the lateral hypothalamic (LH) hunger centre were studied in the presence and absence of food. It was found that in the absence of food the response of the sensorimotor cortical neurons to LH stimulation differed between hungry and fed animals. No changes in firing rate were observed in 50% of neurons in hungry rabbits, and firing was inhibited in 45% of neurons in fed animals. Feeding reinforcement changed the nature of neuronal responses to LH stimulation. Qualitative changes in the responses to LH stimulation were observed in 77% of neurons in hungry rabbits, and in 61% of neurons in fed rabbits. Most neurons increased their rate of firing both in hungry and in fed animals.

A ubiquitous mammalian transcription factor, Oct-1 (also known as OTF-1, NF-A1, OBP100, or NFIII), stimulates the initiation of replication of adenovirus DNA, and may also be involved in the activation of some chromosomal replication origins. If this is true, binding sites for Oct-1 should be present within regions responsible for the initiation of DNA replication. In this study such a binding site has been identified within a 340bp fragment that was originally isolated from a minor fraction of DNA associated with a complexed form of DNA polymerase alpha from nonregenerating rat liver, and which shows autonomous replication sequence activity in a transient transfection assay. Northern blot analysis was used to show that Oct-1 mRNA is induced in regenerating rat liver 6-14 h after hepatectomy.

The interaction of liposomes containing different amounts of cholesterol with low-density lipoproteins from human serum was investigated. The efficiency of the interaction was found to depend on the cholesterol content of the liposomes and was highest for liposomes with the maximum cholesterol:phospholipid molar ratio. These liposomes selectively and effectively interacted with low-density lipoproteins; up to 90% of lipoprotein particles interacted with liposomes in serum. Fusion of particles with liposomes was observed during the interaction.

Intracerebroventricular administration of various doses of neuropeptide Y (NPY) to rats had different effects on their feeding behaviour: the lowest dose (100 ng) decreased food intake, but higher doses (5 micrograms) markedly increased the intake. Prazosin, a selective blocker of alpha 1-adrenergic receptors, suppressed the effect induced by 5 micrograms (but not 100 ng) NPY. No such effect was observed with injections of yohimbine or propranolol. The opiate receptor antagonist, naloxone, blocked the feeding behaviour induced by 5 micrograms NPY without having any other effects on the responses induced by 100 ng NPY. The data obtained testify to heterogeneity within the NPY receptors of the central nervous system. It is concluded that the effects of high doses of NPY on feeding behaviour are mediated, at least in part, by alpha 1-adrenergic receptors.

A flow-injection method for the determination of glucose in serum is presented. It is based on the enzymatic measurement of oxygen consumption detected via oxygen quenching of the luminescence of certain metalloporphyrins. Phosphorescent water-soluble Pt2+ and Pd(2+)-porphyrins have been characterized by luminescence spectroscopy and decay-time measurements in various buffers, and found to be suitable for oxygen detection in biological systems. A new method for the flow-injection analysis of glucose has been developed based on the use of a column of immobilized glucose oxidase and the indicators Pt(2+)-coproporphyrin III and Pd(2+)-coproporphyrin I. The system has been optimized for glucose determination in aqueous samples and in whole serum with the 0.5-200 mM glucose range. Twenty assays can be performed in an hour, and the system has potential for commercial development with biotechnological and medical applications.